Lisa Arzt‐Gradwohl, Eva Schadelbauer, Urban Čerpes, Gudrun Pregartner, Sereina Annik Herzog, Elisabeth Jungwirth, Karin Laipold, Barbara Binder, Gunter J. Sturm
Background Routine allergy diagnostic assessment relies on the patient's medical history, skin testing, and the detection of specific IgE ( sIgE ) in the serum. In addition, molecular allergy diagnostics and the basophil activation test ( BAT ) can be used; however, these additional tests are costly and sometimes time‐consuming. Therefore, our objective was to identify the test with the highest sensitivity, determine the most effective combination of tests to enhance sensitivity, and develop a simple IgE ratio to distinguish between bee and vespid venom allergy in cases of double positivity. Methods We retrospectively analyzed data from 190 bee venom‐allergic and 809 vespid venom‐allergic patients, along with 61 non‐allergic subjects. Sensitivity and specificity were assessed for sIgE ( ImmunoCAP ), the intradermal test ( IDT ), and the BAT . Results Applying a lower cut‐off of 0.1 kU /L in patients with total IgE < 30 kU /L (while keeping the standard cut‐off of 0.35 kU /L otherwise) increased sensitivity for sIgE to bee venom from 85.7% to 94.6% and for vespid venom from 92.2% to 97.0%. The highest sensitivity (100%) was achieved by combining this sIgE dual cut‐off approach with the intradermal test for bee venom allergy, while sensitivity for vespid venom allergy reached 98.5%. A vespid/bee ratio ≥ 2.68 indicated vespid venom allergy with 59.3% sensitivity, while a bee/vespid ratio ≥ 5.33 identified bee venom allergy with 50.6% sensitivity, both with 100% specificity. Conclusions Conventional tests, such as sIgE determination or intradermal testing, are usually sufficient. Combining both increases sensitivity, while additional tests provide no further benefit. Double‐positive findings may often be clarified using a simple sIgE ratio, though sensitivity remains limited.
常规的过敏诊断评估依赖于患者的病史、皮肤试验和血清中特异性IgE (sIgE)的检测。此外,可采用分子过敏诊断和嗜碱性粒细胞激活试验(BAT);然而,这些额外的测试是昂贵的,有时是耗时的。因此,我们的目标是确定灵敏度最高的测试,确定最有效的测试组合来提高灵敏度,并建立一个简单的IgE比率,以区分双阳性情况下蜜蜂和毒蛇毒液过敏。方法回顾性分析190例蜂毒过敏患者和809例毒蛇毒过敏患者以及61例非过敏患者的资料。评估sIgE (ImmunoCAP)、皮内试验(IDT)和BAT的敏感性和特异性。结果在总IgE≤30 kU /L的患者中使用较低的0.1 kU /L(而在其他情况下保持标准的0.35 kU /L), sIgE对蜂毒的敏感性从85.7%提高到94.6%,对蛇毒的敏感性从92.2%提高到97.0%。将这种sIgE双切断方法与蜂毒过敏的皮内试验相结合,灵敏度最高(100%),而对蛇毒过敏的灵敏度达到98.5%。蜂蜂比≥2.68时,敏感性为59.3%;蜂蜂比≥5.33时,敏感性为50.6%,特异性均为100%。结论:常规检查,如sIgE测定或皮内检查,通常是足够的。两者结合会增加灵敏度,而额外的测试则没有进一步的好处。双阳性结果通常可以用简单的sIgE比值来澄清,尽管灵敏度仍然有限。
{"title":"A Straightforward Algorithm for Diagnosing Hymenoptera Venom Allergy and Identifying the Relevant Venom for Immunotherapy","authors":"Lisa Arzt‐Gradwohl, Eva Schadelbauer, Urban Čerpes, Gudrun Pregartner, Sereina Annik Herzog, Elisabeth Jungwirth, Karin Laipold, Barbara Binder, Gunter J. Sturm","doi":"10.1111/all.70154","DOIUrl":"https://doi.org/10.1111/all.70154","url":null,"abstract":"Background Routine allergy diagnostic assessment relies on the patient's medical history, skin testing, and the detection of specific <jats:styled-content style=\"fixed-case\">IgE</jats:styled-content> ( <jats:styled-content style=\"fixed-case\">sIgE</jats:styled-content> ) in the serum. In addition, molecular allergy diagnostics and the basophil activation test ( <jats:styled-content style=\"fixed-case\">BAT</jats:styled-content> ) can be used; however, these additional tests are costly and sometimes time‐consuming. Therefore, our objective was to identify the test with the highest sensitivity, determine the most effective combination of tests to enhance sensitivity, and develop a simple <jats:styled-content style=\"fixed-case\">IgE</jats:styled-content> ratio to distinguish between bee and vespid venom allergy in cases of double positivity. Methods We retrospectively analyzed data from 190 bee venom‐allergic and 809 vespid venom‐allergic patients, along with 61 non‐allergic subjects. Sensitivity and specificity were assessed for <jats:styled-content style=\"fixed-case\">sIgE</jats:styled-content> ( <jats:styled-content style=\"fixed-case\">ImmunoCAP</jats:styled-content> ), the intradermal test ( <jats:styled-content style=\"fixed-case\">IDT</jats:styled-content> ), and the <jats:styled-content style=\"fixed-case\">BAT</jats:styled-content> . Results Applying a lower cut‐off of 0.1 <jats:styled-content style=\"fixed-case\">kU</jats:styled-content> /L in patients with total <jats:styled-content style=\"fixed-case\">IgE</jats:styled-content> < 30 <jats:styled-content style=\"fixed-case\">kU</jats:styled-content> /L (while keeping the standard cut‐off of 0.35 <jats:styled-content style=\"fixed-case\">kU</jats:styled-content> /L otherwise) increased sensitivity for <jats:styled-content style=\"fixed-case\">sIgE</jats:styled-content> to bee venom from 85.7% to 94.6% and for vespid venom from 92.2% to 97.0%. The highest sensitivity (100%) was achieved by combining this <jats:styled-content style=\"fixed-case\">sIgE</jats:styled-content> dual cut‐off approach with the intradermal test for bee venom allergy, while sensitivity for vespid venom allergy reached 98.5%. A vespid/bee ratio ≥ 2.68 indicated vespid venom allergy with 59.3% sensitivity, while a bee/vespid ratio ≥ 5.33 identified bee venom allergy with 50.6% sensitivity, both with 100% specificity. Conclusions Conventional tests, such as <jats:styled-content style=\"fixed-case\">sIgE</jats:styled-content> determination or intradermal testing, are usually sufficient. Combining both increases sensitivity, while additional tests provide no further benefit. Double‐positive findings may often be clarified using a simple <jats:styled-content style=\"fixed-case\">sIgE</jats:styled-content> ratio, though sensitivity remains limited.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"106 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145498261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
P E Vonk,J J Otten,H B E Elzinga,R J L van der Lans,G F J P Adriaensen,L B L Benoist,D R Hoven,W J Fokkens,S Reitsma,
BACKGROUNDDupilumab is effective in treating patients with type-2 dominant chronic rhinosinusitis with nasal polyps (T2-CRSwNP). Dosing starts at an interval of 1×/2 weeks (Q2W) with possible tapering upon disease control. Prolonging the interdose interval reduces patient burden and side effects and improves cost-effectiveness.OBJECTIVES(1) Analyze how many patients successfully reach and maintain extended tapering of at least 1×/12 weeks (Q12W), (2) evaluate differences in baseline characteristics and clinical measurements between patients who maintain disease control on ≥ Q12W ("super-responders") and patients who do not; (3) compare characteristics of "super-responders" to patients reaching Q12W but losing disease control on that dose ("excellent responders").METHODProspective cohort study including dupilumab-treated T2-CRSwNP patients with a minimum follow-up of 2.5 years.RESULTSFrom a total of 198 patients, 28 (14%) were "super-responders", and 26 (13%) "excellent responders." "super-responders" had less comorbid asthma (60.7% vs. 85.9%, p < 0.001), lower baseline immunoglobulin E levels (median [Q1: Q3]: 145 [58.7; 485] vs. 313 [135.5; 746]; p = 0.007) and a shorter time since last sinus surgery (2.5 years [1; 4.8] vs. 4 years [2; 7]; p = 0.026) compared to others. No differences were observed between "excellent" and "super-responders" at baseline, nor at the start of the Q12W interval. "excellent responders" showed worsening of clinical outcomes as well as increases in T2 markers in blood between start and stop of the Q12W interval.CONCLUSIONTapering of dupilumab to once every 12 weeks (Q12W) can be applied to super-responding patients. No clear predisposing factors were identified predicting the feasibility of extended tapering.
背景:dupilumab对2型显性慢性鼻窦炎伴鼻息肉(T2-CRSwNP)患者有效。给药间隔为1×/2周(Q2W),在疾病控制后可能逐渐减少。延长给药间隔可减少患者负担和副作用,并提高成本效益。(1)分析有多少患者成功达到并维持至少1×/12周(Q12W)的延长减量,(2)评估维持≥Q12W(“超级应答者”)疾病控制的患者与未达到Q12W的患者之间基线特征和临床测量的差异;(3)比较“超级应答者”与达到Q12W但在该剂量下失去疾病控制的患者(“优秀应答者”)的特征。方法前瞻性队列研究,纳入dupilumab治疗的T2-CRSwNP患者,随访时间至少为2.5年。结果198例患者中,“超级应答者”28例(14%),“优秀应答者”26例(13%)。“超级应答者”的共病哮喘较少(60.7% vs. 85.9%, p < 0.001),基线免疫球E水平较低(中位数[Q1: Q3]: 145 [58.7; 485] vs. 313 [135.5; 746]; p = 0.007),距上次鼻窦手术时间较短(2.5年[1.4.8]vs. 4年[2.7];p = 0.026)。在基线和Q12W间隔开始时,没有观察到“优秀”和“超级反应”之间的差异。“优秀应答者”表现出临床结果的恶化以及在Q12W间隔开始和停止期间血液中T2标记物的增加。结论dupilumab减量至每12周1次(Q12W)可用于超反应患者。没有明确的诱发因素预测延长锥形的可行性。
{"title":"\"Super-Responders\" to Dupilumab Treatment in Patients With Primary Diffuse Chronic Rhinosinusitis With Nasal Polyps.","authors":"P E Vonk,J J Otten,H B E Elzinga,R J L van der Lans,G F J P Adriaensen,L B L Benoist,D R Hoven,W J Fokkens,S Reitsma, ","doi":"10.1111/all.70151","DOIUrl":"https://doi.org/10.1111/all.70151","url":null,"abstract":"BACKGROUNDDupilumab is effective in treating patients with type-2 dominant chronic rhinosinusitis with nasal polyps (T2-CRSwNP). Dosing starts at an interval of 1×/2 weeks (Q2W) with possible tapering upon disease control. Prolonging the interdose interval reduces patient burden and side effects and improves cost-effectiveness.OBJECTIVES(1) Analyze how many patients successfully reach and maintain extended tapering of at least 1×/12 weeks (Q12W), (2) evaluate differences in baseline characteristics and clinical measurements between patients who maintain disease control on ≥ Q12W (\"super-responders\") and patients who do not; (3) compare characteristics of \"super-responders\" to patients reaching Q12W but losing disease control on that dose (\"excellent responders\").METHODProspective cohort study including dupilumab-treated T2-CRSwNP patients with a minimum follow-up of 2.5 years.RESULTSFrom a total of 198 patients, 28 (14%) were \"super-responders\", and 26 (13%) \"excellent responders.\" \"super-responders\" had less comorbid asthma (60.7% vs. 85.9%, p < 0.001), lower baseline immunoglobulin E levels (median [Q1: Q3]: 145 [58.7; 485] vs. 313 [135.5; 746]; p = 0.007) and a shorter time since last sinus surgery (2.5 years [1; 4.8] vs. 4 years [2; 7]; p = 0.026) compared to others. No differences were observed between \"excellent\" and \"super-responders\" at baseline, nor at the start of the Q12W interval. \"excellent responders\" showed worsening of clinical outcomes as well as increases in T2 markers in blood between start and stop of the Q12W interval.CONCLUSIONTapering of dupilumab to once every 12 weeks (Q12W) can be applied to super-responding patients. No clear predisposing factors were identified predicting the feasibility of extended tapering.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"51 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145491741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
María Salas,Alessandro Ghilarducci,Inmaculada Doña,Michele Schiappoli,Marina Labella,Annarita Dama,Elisa Olivieri,María José Torres,Patrizia Bonadonna
BACKGROUNDDiagnostic strategies for cephalosporin allergy are not well defined due to differences in inclusion criteria among studies and a lack of standardised diagnostic tests. Our aim was to describe the characteristics of patients with a suspicion of cephalosporin allergy and to analyse the role of in vivo tests.METHODSPatients with suspected cephalosporin allergy were prospectively evaluated (2019-2023). Diagnosis was achieved using clinical history, skin tests (STs) and, if negative, drug provocation tests (DPTs). A randomised group of patients who tolerated DPT were retested by STs at 2-8 weeks.RESULTS211 patients were evaluated, with 55.4% reporting IRs and 44.5% NIRs. Skin was involved in half of the patients reporting IRs and in all reporting NIRs (p < 0.0001). Anaphylaxis was experienced by 18% and shock by 7.1%. The cephalosporin most commonly involved was cefuroxime (63.6%) (p < 0.0001) in the Spanish cohort and cefazolin (51%) (p < 0.0001) in the Italian one. Allergy was confirmed in 57.2% of patients reporting IRs (47% by STs and 9.4% by DPT) and 14.9% of NIRs (5.3% by STs and 8.5% by DPT). In the positive-ST group, the percentage of grade II and III reactions was higher (p = 0.02) and the interval reaction-study shorter (p = 0.0007) than in negative-ST. Of the 48 patients retested, 1 (2.9%) who reported an IR and 1 (7.1%) who reported NIR resulted positive.CONCLUSIONSThe patterns of cephalosporin allergy may differ across different regions, being STs and DPT useful for diagnosis. Further studies are needed to confirm the role of retesting, as well as to identify which patients would benefit most from this procedure.
{"title":"Allergological Work-Up in Cephalosporin Allergy Diagnosis and Delabelling: The Experience From Two European Allergy Centres.","authors":"María Salas,Alessandro Ghilarducci,Inmaculada Doña,Michele Schiappoli,Marina Labella,Annarita Dama,Elisa Olivieri,María José Torres,Patrizia Bonadonna","doi":"10.1111/all.70120","DOIUrl":"https://doi.org/10.1111/all.70120","url":null,"abstract":"BACKGROUNDDiagnostic strategies for cephalosporin allergy are not well defined due to differences in inclusion criteria among studies and a lack of standardised diagnostic tests. Our aim was to describe the characteristics of patients with a suspicion of cephalosporin allergy and to analyse the role of in vivo tests.METHODSPatients with suspected cephalosporin allergy were prospectively evaluated (2019-2023). Diagnosis was achieved using clinical history, skin tests (STs) and, if negative, drug provocation tests (DPTs). A randomised group of patients who tolerated DPT were retested by STs at 2-8 weeks.RESULTS211 patients were evaluated, with 55.4% reporting IRs and 44.5% NIRs. Skin was involved in half of the patients reporting IRs and in all reporting NIRs (p < 0.0001). Anaphylaxis was experienced by 18% and shock by 7.1%. The cephalosporin most commonly involved was cefuroxime (63.6%) (p < 0.0001) in the Spanish cohort and cefazolin (51%) (p < 0.0001) in the Italian one. Allergy was confirmed in 57.2% of patients reporting IRs (47% by STs and 9.4% by DPT) and 14.9% of NIRs (5.3% by STs and 8.5% by DPT). In the positive-ST group, the percentage of grade II and III reactions was higher (p = 0.02) and the interval reaction-study shorter (p = 0.0007) than in negative-ST. Of the 48 patients retested, 1 (2.9%) who reported an IR and 1 (7.1%) who reported NIR resulted positive.CONCLUSIONSThe patterns of cephalosporin allergy may differ across different regions, being STs and DPT useful for diagnosis. Further studies are needed to confirm the role of retesting, as well as to identify which patients would benefit most from this procedure.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"54 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145491745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kirandeep K. Gill, Carolina Moore, Onyekachi Nwogu, John W. Kroner, Wan‐Chi Chang, Jeffrey Burkle, Samuel J. Virolainen, Mariana L. Stevens, Asel Baatyrbek, Emily R. Miraldi, Jocelyn M. Biagini, Ashley L. Devonshire, Leah Kottyan, Justin T. Schwartz, Amal H. Assa'ad, Lisa J. Martin, Sandra Andorf, Gurjit K. Khurana Hershey, Krishna M. Roskin
IgE B cells produce antibodies responsible for the inappropriate specificity seen in allergic disease. In this study, we sequence antibody gene repertoires from a large, well‐characterized early life cohort at risk for developing food allergy. We found that food allergen sensitization was associated with lower IgE mutation frequencies that was abrogated in children living with a pet dog, suggesting potential molecular mechanisms underlying the hygiene hypothesis (i.e., protective effects of pet ownership and non‐antiseptic environs reported for allergic disease). We also observed increased IgE diversity and increased isotype‐switching to IgE, suggesting that B‐cell development is altered in those with food allergen sensitizations relative to those without. IgE diversity was even more extreme in subjects who were highly likely to be peanut allergic. Unlike food sensitization, we detected no effect of aeroallergen sensitization on IgE mutation levels and diversity. Consistent patterns of antibody rearrangement were associated with food allergen sensitization. These results have important implications for the allergic response driven by mast cells and basophils and the underlying drivers of the atopic march.
{"title":"B‐Cell Repertoire of Children With Atopic Dermatitis Exhibits Altered IgE Maturation Associated With Allergic Food Sensitization","authors":"Kirandeep K. Gill, Carolina Moore, Onyekachi Nwogu, John W. Kroner, Wan‐Chi Chang, Jeffrey Burkle, Samuel J. Virolainen, Mariana L. Stevens, Asel Baatyrbek, Emily R. Miraldi, Jocelyn M. Biagini, Ashley L. Devonshire, Leah Kottyan, Justin T. Schwartz, Amal H. Assa'ad, Lisa J. Martin, Sandra Andorf, Gurjit K. Khurana Hershey, Krishna M. Roskin","doi":"10.1111/all.70150","DOIUrl":"https://doi.org/10.1111/all.70150","url":null,"abstract":"IgE B cells produce antibodies responsible for the inappropriate specificity seen in allergic disease. In this study, we sequence antibody gene repertoires from a large, well‐characterized early life cohort at risk for developing food allergy. We found that food allergen sensitization was associated with lower IgE mutation frequencies that was abrogated in children living with a pet dog, suggesting potential molecular mechanisms underlying the hygiene hypothesis (i.e., protective effects of pet ownership and non‐antiseptic environs reported for allergic disease). We also observed increased IgE diversity and increased isotype‐switching to IgE, suggesting that B‐cell development is altered in those with food allergen sensitizations relative to those without. IgE diversity was even more extreme in subjects who were highly likely to be peanut allergic. Unlike food sensitization, we detected no effect of aeroallergen sensitization on IgE mutation levels and diversity. Consistent patterns of antibody rearrangement were associated with food allergen sensitization. These results have important implications for the allergic response driven by mast cells and basophils and the underlying drivers of the atopic march.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"80 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145484664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pauline J M Kuks,Tatiana Karp,Jorine E Hartman,Monica Kraft,Salman Siddiqui,Leonardo M Fabbri,Bianca Beghé,Klaus F Rabe,Alberto Papi,Christopher E Brightling,Dave Singh,Xingnan Li,Janwillem W H Kocks,Ulrica Scaffidi-Argentina,Huib A M Kerstjens,Irene H Heijink,Simon D Pouwels,Dirk-Jan Slebos,Maarten van den Berge
BACKGROUNDPrevious cluster analyses have identified subgroups of asthma. However, only a few studies included parameters of small airways dysfunction (SAD), or gene expression profiles reflecting underlying disease mechanisms. We aimed to identify clinically distinct asthma phenotypes, beyond GINA asthma severity, using available data from the ATLANTIS study which focused on identifying the prevalence of SAD in asthma and its role in asthma control, exacerbations and quality of life.METHODSThe ATLANTIS study included 773 asthma patients (mean age 44 years, 58% female, 76% never-smoker, GINA 1-5). Subjects were extensively characterized, including symptoms, parameters of large and small airways dysfunction, blood and sputum differential cell counts, and genome-wide gene expression profiling from nasal brushes. Clusters were generated using the Self-Organizing Map-Ward's method.RESULTSFour distinct clusters were identified: A (N = 62; 8%) characterized by the most frequent exacerbations, lower post-bronchodilator FEV1 % predicted, more small airways dysfunction, higher sputum and blood eosinophils, and high expression of asthma-related genes. B (N = 206; 27%) consisting of atopic patients with early-onset asthma, uncontrolled symptoms, and normal lung function and bronchial hyperresponsiveness, along with a high expression of asthma-related genes in the nasal epithelium. C (N = 277; 36%), predominantly male former smokers, with well-controlled asthma, mild obstructive lung disease, and relatively high neutrophil levels. D (N = 228; 29%), with normal lung function and low blood and sputum eosinophils.CONCLUSIONSFour distinct clusters were identified, where the presence of SAD was associated with high type-2 inflammation, lower lung function, and frequent exacerbations. SAD may be a marker of poorly controlled asthma and should be considered as an important clinical trait.
{"title":"Cluster Analysis to Identify Distinct Asthma Phenotypes in the ATLANTIS Cohort.","authors":"Pauline J M Kuks,Tatiana Karp,Jorine E Hartman,Monica Kraft,Salman Siddiqui,Leonardo M Fabbri,Bianca Beghé,Klaus F Rabe,Alberto Papi,Christopher E Brightling,Dave Singh,Xingnan Li,Janwillem W H Kocks,Ulrica Scaffidi-Argentina,Huib A M Kerstjens,Irene H Heijink,Simon D Pouwels,Dirk-Jan Slebos,Maarten van den Berge","doi":"10.1111/all.70127","DOIUrl":"https://doi.org/10.1111/all.70127","url":null,"abstract":"BACKGROUNDPrevious cluster analyses have identified subgroups of asthma. However, only a few studies included parameters of small airways dysfunction (SAD), or gene expression profiles reflecting underlying disease mechanisms. We aimed to identify clinically distinct asthma phenotypes, beyond GINA asthma severity, using available data from the ATLANTIS study which focused on identifying the prevalence of SAD in asthma and its role in asthma control, exacerbations and quality of life.METHODSThe ATLANTIS study included 773 asthma patients (mean age 44 years, 58% female, 76% never-smoker, GINA 1-5). Subjects were extensively characterized, including symptoms, parameters of large and small airways dysfunction, blood and sputum differential cell counts, and genome-wide gene expression profiling from nasal brushes. Clusters were generated using the Self-Organizing Map-Ward's method.RESULTSFour distinct clusters were identified: A (N = 62; 8%) characterized by the most frequent exacerbations, lower post-bronchodilator FEV1 % predicted, more small airways dysfunction, higher sputum and blood eosinophils, and high expression of asthma-related genes. B (N = 206; 27%) consisting of atopic patients with early-onset asthma, uncontrolled symptoms, and normal lung function and bronchial hyperresponsiveness, along with a high expression of asthma-related genes in the nasal epithelium. C (N = 277; 36%), predominantly male former smokers, with well-controlled asthma, mild obstructive lung disease, and relatively high neutrophil levels. D (N = 228; 29%), with normal lung function and low blood and sputum eosinophils.CONCLUSIONSFour distinct clusters were identified, where the presence of SAD was associated with high type-2 inflammation, lower lung function, and frequent exacerbations. SAD may be a marker of poorly controlled asthma and should be considered as an important clinical trait.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"217 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145477496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bjarke Hviid-Vyff,Søren Helbo Skaarup,Amber Duin,Johannes Martin Schmid,Hans Jürgen Hoffmann
{"title":"Low-Dose Intralymphatic Immunotherapy for Grass Pollen Allergy is Both Safe and Effective.","authors":"Bjarke Hviid-Vyff,Søren Helbo Skaarup,Amber Duin,Johannes Martin Schmid,Hans Jürgen Hoffmann","doi":"10.1111/all.70148","DOIUrl":"https://doi.org/10.1111/all.70148","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":"169 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145477441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction to \"Deciphering Dysfunctional Regulatory T Cells in Atopic Dermatitis\".","authors":"","doi":"10.1111/all.70156","DOIUrl":"https://doi.org/10.1111/all.70156","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":"136 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145477453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
James King, Ashley Woodcock, Antonio Anzueto, Alexander J. K. Wilkinson, Christer Janson, Richard Henderson, Sourabh Fulmali, Maximilian Plank
Background Rapid reductions in greenhouse gas (GHG) emissions are vital to combat climate change. Healthcare systems contribute ~5% of global GHG emissions, with pressurised metered‐dose inhalers (pMDIs) a significant contributor owing to their hydrofluorocarbon propellants. This study compared GHG emissions of a salbutamol pMDI using a low‐carbon propellant in clinical development, hydrofluoroalkane (HFA)‐152a, against current salbutamol inhalers. Methods Three ‘cradle‐to‐grave’ lifecycle analyses compared GHG emissions of salbutamol pMDIs with HFA‐152a and HFA‐134a, and salbutamol dry‐powder inhaler (DPI). Over 600 individual emission factors were calculated from > 2000 data points, and categorised into Active Pharmaceutical Ingredients Manufacture, Micronisation, Device, Formulation/Packaging, Use, Distribution and End‐of‐Life stages. 2023 manufacturing and supply data were collected from Algeria, Australia, Canada, France, Poland, Romania and Saudi Arabia. Carbon footprints were independently verified by the Carbon Trust. Results Mean total carbon footprint per salbutamol inhaler (based on 100‐year global warming potential [GWP100]) was 26.91, 2.06 and 0.69 kgCO 2 e for HFA‐134a pMDI, HFA‐152a pMDI and DPI, respectively. This equated to a 92% reduction in total emissions for HFA‐152a versus HFA‐134a. Most pMDI emissions came from the Use stage (HFA‐134a: 21.48 kgCO 2 e; HFA‐152a: 1.45 kgCO 2 e). Per actuation, emissions were 135, 10 and 11 gCO 2 e, respectively. For each pMDI, GHG emissions were similar across countries. Conclusions The low‐GWP propellant, HFA‐152a is expected to achieve > 90% reduction in the carbon footprint of salbutamol pMDI versus the currently used HFA‐134a. The development of salbutamol pMDI with HFA‐152a is a crucial step towards ensuring future patient access to salbutamol in a pMDI.
{"title":"Decarbonising Respiratory Care: The Impact of a Low‐Carbon Salbutamol Pressurised Metered‐Dose Inhalers","authors":"James King, Ashley Woodcock, Antonio Anzueto, Alexander J. K. Wilkinson, Christer Janson, Richard Henderson, Sourabh Fulmali, Maximilian Plank","doi":"10.1111/all.70141","DOIUrl":"https://doi.org/10.1111/all.70141","url":null,"abstract":"Background Rapid reductions in greenhouse gas (GHG) emissions are vital to combat climate change. Healthcare systems contribute ~5% of global GHG emissions, with pressurised metered‐dose inhalers (pMDIs) a significant contributor owing to their hydrofluorocarbon propellants. This study compared GHG emissions of a salbutamol pMDI using a low‐carbon propellant in clinical development, hydrofluoroalkane (HFA)‐152a, against current salbutamol inhalers. Methods Three ‘cradle‐to‐grave’ lifecycle analyses compared GHG emissions of salbutamol pMDIs with HFA‐152a and HFA‐134a, and salbutamol dry‐powder inhaler (DPI). Over 600 individual emission factors were calculated from > 2000 data points, and categorised into Active Pharmaceutical Ingredients Manufacture, Micronisation, Device, Formulation/Packaging, Use, Distribution and End‐of‐Life stages. 2023 manufacturing and supply data were collected from Algeria, Australia, Canada, France, Poland, Romania and Saudi Arabia. Carbon footprints were independently verified by the Carbon Trust. Results Mean total carbon footprint per salbutamol inhaler (based on 100‐year global warming potential [GWP100]) was 26.91, 2.06 and 0.69 kgCO <jats:sub>2</jats:sub> e for HFA‐134a pMDI, HFA‐152a pMDI and DPI, respectively. This equated to a 92% reduction in total emissions for HFA‐152a versus HFA‐134a. Most pMDI emissions came from the Use stage (HFA‐134a: 21.48 kgCO <jats:sub>2</jats:sub> e; HFA‐152a: 1.45 kgCO <jats:sub>2</jats:sub> e). Per actuation, emissions were 135, 10 and 11 gCO <jats:sub>2</jats:sub> e, respectively. For each pMDI, GHG emissions were similar across countries. Conclusions The low‐GWP propellant, HFA‐152a is expected to achieve > 90% reduction in the carbon footprint of salbutamol pMDI versus the currently used HFA‐134a. The development of salbutamol pMDI with HFA‐152a is a crucial step towards ensuring future patient access to salbutamol in a pMDI.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"10 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145454712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rasmus K. Jensen, Michaela Miehe, Rosaria Gandini, Martin H. Jørgensen, Edzard Spillner, Gregers R. Andersen
Background IgE is the central driver of allergic responses. Prior studies have defined the conformation of the IgE Fc fragment bound to the FcεRIα ectodomain and the dynamic properties of the IgE Fc. It remains unknown, how these prior studies translate to the complex of a full antibody including the Fab arms with the receptor. Methods For structural analysis, crystallography, cryo‐EM and negative stain EM (ns‐EM) were combined. IgE variants were analyzed by mediator release and CD23 binding assays. Results An ensemble of 10 cryo‐EM structures of the full‐size IgE FcεRIα complex was obtained revealing that the receptor bound IgE adopts a pronounced T‐like conformation. Either Fab arm may rotate up to 40°. Two additional conformations with different arrangements of the Fab arms were captured in ns‐EM. The introduction of additional flexibility into the Fab‐Fc hinge does not compromise the biological activity of IgE, suggesting that the observed conformations of the IgE Fab‐Fc hinge exhibit equivalent biological function. Comparison of the full IgE receptor complex with recent cryo‐EM structures of the intact receptor reveals that FcεRI conformations differ markedly by the orientation of the ectodomain. Hence, our ensemble of IgE FcεRIα structures including the Fab arms enabled critical evaluation of FcεRI conformations. Conclusion Our data reveal the architecture of a full‐size IgE antibody bound to its receptor and a new layer of dynamics in FcεRIα bound IgE on top of the well‐established IgE Fc conformations. Development of novel anti‐IgE therapeutics may take into account these properties of FcεRIα bound IgE.
IgE是过敏反应的主要驱动因素。先前的研究已经确定了IgE Fc片段与Fcε ri α外畴结合的构象和IgE Fc的动态特性。目前尚不清楚,这些先前的研究如何转化为一个完整的抗体复合物,包括Fab臂与受体。方法采用晶体学、低温电镜和阴性染色电镜(ns - EM)相结合的方法进行结构分析。通过介质释放和CD23结合试验分析IgE变异。结果获得了全尺寸IgE FcεRIα复合物的10个低温电镜结构,表明受体结合的IgE具有明显的T - like构象。Fab臂可以旋转40°。在ns - EM中还捕获了另外两种具有不同排列方式的Fab臂构象。在Fab - Fc铰链中引入额外的柔韧性不会损害IgE的生物活性,这表明观察到的IgE Fab - Fc铰链的构象具有等效的生物功能。将完整的IgE受体复合物与最近完整受体的低温电镜结构进行比较,发现FcεRI构象在外畴的取向上有明显的不同。因此,我们的IgE FcεRIα结构集合(包括Fab臂)能够对FcεRI构象进行批判性评估。结论我们的数据揭示了一个与受体结合的全尺寸IgE抗体的结构,以及在已建立的IgE Fc构象之上的Fcε ri α结合IgE的新动态层。新型抗IgE药物的开发可能会考虑到FcεRIα结合IgE的这些特性。
{"title":"Cryo‐EM Structure of FcεRI Bound IgE Reveals Multiple Defined Conformations of the Fab‐Fc Hinge","authors":"Rasmus K. Jensen, Michaela Miehe, Rosaria Gandini, Martin H. Jørgensen, Edzard Spillner, Gregers R. Andersen","doi":"10.1111/all.70132","DOIUrl":"https://doi.org/10.1111/all.70132","url":null,"abstract":"Background IgE is the central driver of allergic responses. Prior studies have defined the conformation of the IgE Fc fragment bound to the FcεRIα ectodomain and the dynamic properties of the IgE Fc. It remains unknown, how these prior studies translate to the complex of a full antibody including the Fab arms with the receptor. Methods For structural analysis, crystallography, cryo‐EM and negative stain EM (ns‐EM) were combined. IgE variants were analyzed by mediator release and CD23 binding assays. Results An ensemble of 10 cryo‐EM structures of the full‐size IgE FcεRIα complex was obtained revealing that the receptor bound IgE adopts a pronounced T‐like conformation. Either Fab arm may rotate up to 40°. Two additional conformations with different arrangements of the Fab arms were captured in ns‐EM. The introduction of additional flexibility into the Fab‐Fc hinge does not compromise the biological activity of IgE, suggesting that the observed conformations of the IgE Fab‐Fc hinge exhibit equivalent biological function. Comparison of the full IgE receptor complex with recent cryo‐EM structures of the intact receptor reveals that FcεRI conformations differ markedly by the orientation of the ectodomain. Hence, our ensemble of IgE FcεRIα structures including the Fab arms enabled critical evaluation of FcεRI conformations. Conclusion Our data reveal the architecture of a full‐size IgE antibody bound to its receptor and a new layer of dynamics in FcεRIα bound IgE on top of the well‐established IgE Fc conformations. Development of novel anti‐IgE therapeutics may take into account these properties of FcεRIα bound IgE.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"10 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145455317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Supinda Bunyavanich, Mubeccel Akdis, M. Cecilia Berin, Alexander Eggel, Sarita U. Patil, Mohamed H. Shamji, Juan‐Felipe López, Hugh A. Sampson
The double‐blind placebo‐controlled oral food challenge (DBPCFC) has been the “gold standard” for diagnosing IgE‐mediated food allergy for the past 50 years. Despite tremendous strides in our understanding of basic mechanisms and clinical features of food allergy, we remain dependent on refinements of old technologies, i.e., skin tests and serum IgE measurements, to complement clinical history in making an accurate diagnosis of food allergies. However, recent technical advances in two effector cell assays, i.e., the basophil and mast cell activation tests, may soon bring these diagnostic biomarkers to the clinic. In addition, new advances in antibody assays, T‐cell assays, transcriptomics, and metabolomics in conjunction with machine learning and artificial intelligence may soon enable us to diagnose food allergy and accurately monitor immunotherapeutic outcomes without the need for an oral food challenge.
{"title":"Novel Biomarkers and Diagnostic Tools in Food Allergy","authors":"Supinda Bunyavanich, Mubeccel Akdis, M. Cecilia Berin, Alexander Eggel, Sarita U. Patil, Mohamed H. Shamji, Juan‐Felipe López, Hugh A. Sampson","doi":"10.1111/all.70133","DOIUrl":"https://doi.org/10.1111/all.70133","url":null,"abstract":"The double‐blind placebo‐controlled oral food challenge (DBPCFC) has been the “gold standard” for diagnosing IgE‐mediated food allergy for the past 50 years. Despite tremendous strides in our understanding of basic mechanisms and clinical features of food allergy, we remain dependent on refinements of old technologies, i.e., skin tests and serum IgE measurements, to complement clinical history in making an accurate diagnosis of food allergies. However, recent technical advances in two effector cell assays, i.e., the basophil and mast cell activation tests, may soon bring these diagnostic biomarkers to the clinic. In addition, new advances in antibody assays, T‐cell assays, transcriptomics, and metabolomics in conjunction with machine learning and artificial intelligence may soon enable us to diagnose food allergy and accurately monitor immunotherapeutic outcomes without the need for an oral food challenge.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"168 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145447303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}